Abstract The salivary gland ducts serve as an epithelial barrier between secretory components of the gland and the oral cavity. An essential function of such a barrier is the detection and response to external insults. In many tissues, scattered single chemosensory cells (SCCs) function as sentinels, which relay external cues into transduced signals that activate an immune response. In both mouse and human salivary glands, we have found distinct solitary duct cells that co-express components of chemosensory signaling pathways, including Nkcc1, IP3R3, and Plc2. In the mouse, these cells are marked by expression of the transcription factor Ascl3. The observation that these morphologically distinct cells exhibit molecular characteristics resembling SCCs suggests that they fulfill a specialized function. This proposal will explore our hypothesis that SCCs are active in mouse and human salivary glands, and are involved in detection and transduction of external stimuli to surrounding cells, and perhaps to neurons. We speculate that Ascl3 expression marks a type of SCCs in the mouse salivary gland, and will investigate whether this is the case in human glands as well. We expect that SCCs play a critical role in mounting an immune response in the salivary glands, and may be involved in the mechanisms leading to acute and chronic inflammation.